Research - Liver Perfusion
Perfusion of porcine livers using ex-vivo whole organ liver perfusion system
Background
Acute liver failure (ALF) is a disease with a high mortality ranging from 60-90% even with the best medical management. The only effective treatment is orthotopic liver transplant (OLT), which improves survival from approximately 20 to 50–70%. The demand for organs, however, has increased to the point where up to a third of patients with acute liver failure will die before a donor liver becomes available. A variety of approaches have been developed for providing temporary liver support to bridge the patient with liver failure to OLT or to buy time for liver to regenerate. A liver support device may also play a role in allowing resection of more than 75% of the non-cirrhotic liver safely in humans.
Biological support devices consist of extracorporeal hepatocytes (porcine/ human hepatoblastoma cell line) in a synthetic framework. Bioartioficial livers (BAL) with hepatocytes attached to collagen-coated microcarriers or cultured in multiplated monolayers or entrapped in hydrogels have all been tried, however to date none of these have been demonstrated to reduce mortality in acute hepatic failure. A bio-artificial liver capable of providing life-supporting function has to have at least 400 grams hepatocytes and advanced tissue culture techniques are essential to maintain their viability and function. The need for hepatic tissue for effective treatment of patients with ALF led to the concept of using the whole liver in an extracorporeal perfusion system.
Extracorporeal whole liver perfusion
A liver perfused with autologous blood appropriately oxygenated and augmented with nutrients contains hepatocytes in a near ideal culture medium. Thus, the principal problems with creating a bioreactor with enough biomass of functioning hepatocytes are overcome. Experimental models of extracorporeal perfusion of porcine livers can maintain a viable and functioning organ successfully for upto 72 hours with the use of high quality pediatric cardiopulmonary bypass components. The incorporation of a hollow fibre dialysis filter in this model with an effective pore size of 80-100 kDa allows filtration of toxins and metabolites across the membrane while providing immunoprotection against the theoretical risk of transfer of porcine retroviruses. With these modifications, it is suitable for use as a liver support device.
In our study, pig livers will be subjected to the normothermic perfusion apparatus with incorporated dialysis units. The perfusion circuit to support of the liver will be in essence a cardiopulmonary bypass circuit.
Basic components of the circuit would be:
• Oxygenator
• Heat exchanger
• Centrifugal pump
• Reservoir
• Pressure transducers
• Flow probes
Figure 1: Liver Persusion circuit 
Autologous heparinised blood will be oxygenated and warmed with a paediatric oxygenator heat exchanger unit. It will then be perfused through the hepatic artery and portal vein. Hepatic function will be assessed by the addition of test substances and measurement of metabolites accumulating, or the test substance concentration decreasing.
In future, this extracorporeal liver perfusion model might prove to be a physiological, successful, and cost effective therapy for the treatment of patients with acute, but reversible hepatic failure, as well as for patients awaiting liver transplantation.
